Oxygen therapy is frequently required for patients with acute lung injury. Paradoxically, administration of high concentrations of oxygen to such patients, while necessary, may itself result in hyperoxic lung injury. The mechanisms underlying hyperoxic lung injury are not clear. The neutrophil, frequently present in lung pathology specimens in animals exposed to increased oxygen concentrations, may play a role in such injury. In order to better define the neutrophil's contribution to the pathogenesis of hyperoxic lung injury, we are conducting a study evaluating the effects of administration of either granulocyte colony stimulation factor (G-CSF) or monoclonal antibodies (MAb) directed against neutrophil and endothelial adhesion molecules, in animals undergoing periods of increased oxygen exposure. G-CSF is known to increase circulating number and function and has the potential to aggravate hyperoxic lung injury if neutrophil mediated. MAb's to neutrophil and endothelial adhesion proteins on the other hand, have been shown to be protective in various forms of neutrophil mediated tissue injury and may suppress neutrophil mediated lung injury if this occurs during hyperoxic lung exposure. Both G-CSF and adhesion molecule MAb's have been proposed as potential therapies for certain types of patients who may also require oxygen therapy. It will be important to determine how each of these therapies might effect lung function during increased levels of oxygen exposure.